Acute Disseminated Encephalomyelitis in Children

S. N. Krishna Murthy, MD*‡§; Howard S. Faden, MD‡ʈ; Michael E. Cohen, MD*‡§; and Rohit Bakshi, MD*¶#

ABSTRACT. Objective. To describe the epidemio- cute disseminated encephalomyelitis logic, clinical, neuroimaging, and laboratory features; (ADEM) is considered a monophasic acute treatment; and outcome in a cohort of children with acute demyelinating disorder of the central ner- disseminated encephalomyelitis (ADEM). A vous system (CNS) characterized by diffuse neuro- Methods. A 6-year retrospective chart review of chil- logic signs and symptoms coupled with evidence of dren with the diagnosis of ADEM was conducted. multifocal lesions of demyelination on neuroimag- Results. Eighteen cases were identified. Sixteen pa- tients (88%) presented in either winter or spring. Thir- ing. The epidemiology of ADEM has changed since 1 teen children (72%) had a recent upper respiratory tract its original description by Lucas in the early 18th illness. Patients presented most often with motor deficits century. At that time, ADEM commonly followed (77%) and secondly with altered consciousness (45%). common childhood infections such as measles, Spinal fluid abnormalities occurred in 70%. Despite rig- smallpox, and chickenpox and was associated with orous microbiologic testing, a definite microbiologic di- significant mortality and morbidity. In a series of agnosis was established only in 1 child with Epstein-Barr case reports in 1931 in The Lancet, McAlpine2 de- virus disease and probable or possible diagnoses in 3 scribed 3 sets of patients with ADEM: 1) postvacci- children with Bartonella henselae, Mycoplasma pneu- nation, 2) after infectious fevers such as in measles, moniae, or rotavirus disease. Brain magnetic resonance and 3) spontaneous. Those with spontaneous and imaging identified lesions in the cerebral cortex in 80%, in subcortical white matter in 93%, in periventricular postvaccination ADEM did well despite the lack of white matter in 60%, in deep gray matter in 47%, and in antibiotics, steroids, and intensive care facilities, brainstem in 47% of patients. Eleven patients (61%) were whereas those with an infectious cause fared poorly. treated with corticosteroids, and 2 were treated with in- A number of recent reports of ADEM in children travenous immunoglobulins. All patients survived. have confirmed the observations of McAlpine.3,4 Three patients (17%) had long-term neurologic sequelae. Several articles suggested that improved outcome of Conclusions. Epidemiologic evidence from this study ADEM was attributable mainly to the use of steroids; suggests an infectious cause for ADEM. The agent is however, evidence for this was mainly anecdotal.5,6 most likely a difficult-to-diagnose winter/spring respira- The purpose of the present study was to review tory virus. Magnetic resonance imaging was the neuro- ADEM from a single institution with an emphasis on imaging study of choice for establishing the diagnosis and for following the course of the disease. Prognosis for the relationship of clinical features, microbiology, survival and outcome was excellent. Recurrent episodes neuroimaging, and treatment to clinical outcome. of ADEM must be differentiated from multiple sclerosis. Eighteen patients with ADEM were identified. Re- Pediatrics 2002;110:e0–e0. URL: www.pediatrics.org/cgi/ spiratory infections preceded the neurologic presen- doi/10.1542/peds.; acute disseminated encephalomyelitis, tation in the vast majority. Although in most cases a ADEM, encephalitis, postinfectious encephalitis, encepha- specific cause could not be identified, the outcome lomyelitis. was good regardless of treatment.

ABBREVIATIONS. ADEM, acute disseminated encephalomyelitis; METHODS CNS, central nervous system; MRI, magnetic resonance imaging; The inpatient database of Children’s Hospital of Buffalo was FLAIR, fluid-attenuated inversion recovery; PCR, polymerase broadly searched for patients with the diagnosis of ADEM, viral chain reaction; EBV, Epstein-Barr virus; Ig, immunoglobulin; TR, encephalitis, postinfectious encephalitis, encephalomyelitis, and repetition time; TE, echo time; NSA, number of signal averages; transverse myelitis. Sixty-seven cases that occurred between Jan- FOV, field of view; CT, computerized tomography; WBC, white uary 1995 and March 2001 were identified. The diagnosis of blood cell; CSF, cerebrospinal fluid; IVIG, intravenous gamma- ADEM was based on the acute onset of neurologic signs and globulin; MS, multiple sclerosis. symptoms together with magnetic resonance imaging (MRI) evi- dence of multifocal, hyperintense lesions on fluid-attenuated in- version recovery (FLAIR) and T2-weighted images. Of the 67 From the Departments of *Neurology and ‡Pediatrics, State University of patients, 18 patients fulfilled the diagnostic criteria for ADEM. New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, Clinical information was obtained from the inpatient case New York; Divisions of §Child Neurology and ࿣Infectious Diseases, Chil- records. Microbiologic data were extracted from laboratory re- dren’s Hospital of Buffalo, Buffalo, New York; and ¶Imaging Services and ports and progress notes in the individual charts. Records main- the #Buffalo Neuroimaging Analysis Center, Jacobs Neurological Institute tained in the microbiology laboratories were reviewed for any of Kaleida Health, Buffalo, New York. tests performed beginning 1 month before admission to the hos- Received for publication Dec 18, 2001; accepted Apr 8, 2002. pital and ending 1 month after discharge. The specific tests re- Reprint requests to (H.S.F.) Division of Infectious Diseases, Children’s viewed included cultures for bacteria, viruses, and fungi; fluores- Hospital of Buffalo, 219 Bryant St, Buffalo, NY 14222. E-mail: cent antibody tests for respiratory viruses; polymerase chain [email protected] reaction (PCR) tests for enteroviruses, herpes simplex virus, Ep- PEDIATRICS (ISSN 0031 4005). Copyright © 2002 by the American Acad- stein-Barr virus (EBV), and Mycoplasma pneumoniae; enzyme- emy of Pediatrics. linked immunosorbent assay for rotavirus; and immunoglobulin

http://www.pediatrics.org/cgi/content/full/110/2/Downloaded from www.aappublications.org/newse1 by guestPEDIATRICS on September 24, Vol. 2021 110 No. 2 August 2002 e1 G (IgG) and IgM antibody tests for viruses and M pneumoniae.To TABLE 1. Clinical Features of ADEM in 18 Patients ascertain the clinical relevance of the microbiologic test results, we interpreted them in relation to the history of the present illness, n (%) the medical history, and the physical examination. In the case of Systemic signs and symptoms antibody titers, IgM-specific antibody levels, rising IgG-specific Fever 7 (38.5) antibody levels, or relatively high single IgG-specific antibody Nausea and/or vomiting 5 (27.5) levels were considered significant. An infectious diagnosis was Headache 4 (22.5) classified as definite, probable, possible, or not diagnostic on the Stiff neck 1 (5.5) basis of the interpretation of the microbiologic test results. Neurological signs and symptoms All head MRI scans were performed with a uniform protocol on Motor deficits* 14 (77) an inpatient 1.5-T unit (Philips Gyroscan ACS-NT, Best, the Neth- Altered consciousness 8 (44.5) erlands). The protocol included axial conventional spin-echo T1- Sensory deficits 5 (27.5) weighted images before and after a single dose (0.1 mmol/kg) of Urinary symptoms 5 (27.5) gadolinium contrast (repetition time/echo time [TR/TE]: 450/20, Cranial neuropathy† 4 (22.5) ϫ 5-mm thickness, 0.5-mm gaps, 205 256 matrix size, number of Seizures 3 (16.5) signal averages [NSA] 1, field of view [FOV] 23 cm, scanning time Nystagmus 2 (11) 2:59), axial fast spin-echo T2-weighted images (TR/TE: 5000/100, Internuclear ophthalmoplegia 2 (11) ϫ 6-mm, 0.6-mm gaps, 245 256, NSA 3, FOV 23 cm, 15 echoes, Aphasia 1 (5.5) scanning time 3:20), and axial fast spin-echo FLAIR images (TR/ TE/TI: 8000/120/2300, 5-mm, 1.0-mm gaps, 140 256, NSA 2, FOV * Ataxia (7), paraparesis (4), hemiparesis (2), and monoparesis (1). 23 cm, 21 echoes, scanning time 3:12). Sagittal and coronal T1 and † Optic, oculomotor, abducens, and facial nerves. FLAIR images were also performed. Diffusion-weighted imaging and magnetization transfer imaging were not performed. Spinal MRI of the cervical and thoracic cord included T1- and T2- history of upper respiratory tract illness 2 days to 4 weighted axial and sagittal and postcontrast T1 imaging. The hard copies of brain and spine MRI and brain computerized tomogra- weeks before presentation. An average of 10 days phy (CT) scans of all patients were obtained and reread by an occurred between the upper respiratory tract illness experienced neuroimager without knowledge of clinical involve- and the appearance of neurologic symptoms. None ment (R.B.). All studies were available for review except for MRI of the patients had vaccinations in the 3 months of the head of 2 patients and of the spine of 1 patient. The imaging before presentation. Details of the clinical presenta- assessment included quantification of T2/FLAIR lesions and their size and location and the presence of mass effect and enhance- tion are presented in Table 1. Nonspecific signs or ment. Spinal MRI scans available for 5 patients were also re- symptoms of systemic illness, such as fever, head- viewed. Follow-up scans were reviewed for degree of improve- ache, nausea, and vomiting, occurred in 74% of pa- ment, new lesions, and enhancement. Detailed neuroimaging tients (14 of 18). Motor deficits, the most common features with extensive illustration are being prepared for a sep- arate publication. presenting signs/symptoms, included ataxia, para- Clinical follow-up information was obtained from outpatient paresis, hemiparesis, and monoparesis. Altered con- records maintained in the neurology department. Data of patients sciousness was the second most common neurologic not seen in follow-up in the neurology clinics were obtained by sign/symptom. Five patients had urinary symptoms, telephone interviews. which included retention of urine in 4 and inconti- RESULTS nence in 1. Paraparesis, sensory deficits, and urinary symptoms occurred predominantly in patients with Clinical Information spinal cord disease as seen on MRI images. The records of all 18 patients were reviewed. The patients ranged in age from 2.5 years to 22 years with Laboratory Studies a mean of 7.5 years and a median of 7 years. There The white blood cell (WBC) count ranged between were 11 male and 7 female patients. The cases oc- 3200 and 25 100/mm3 with a mean of 11 300 cells/ curred in a seasonal distribution with 88% (16 of 18) mm3. Seven patients (38.9%) had significant in- presenting in winter and spring (December to May; creases in WBC counts. Erythrocyte sedimentation Fig 1). Only 1 case (6%) occurred in summer and 2 rates were elevated in 5 of 12 patients (41.7%). Cere- (12%) in late fall. Clustering of cases occurred in 1997 brospinal fluid (CSF) was analyzed in 17. The CSF and 2000. No cases occurred in 1996 or 1998. was not obtained in 1 patient because of the presence Seventy-two percent of patients (13 of 18) had a of a mass effect on CT scan. CSF evidence of inflam- mation (either pleocytosis or elevated protein) was present in 12 patients (70%). The CSF WBC count ranged between 0 and 137 with a mean of 40.8 cells/ mm3. WBC count was elevated in 7 (39%). The CSF protein ranged between 45 mg/dL and 120 mg/dL with a mean of 73.9 mg/dL. The CSF protein was elevated in 10 patients (55%). CSF glucose concentra- tions were normal in all patients. Oligoclonal bands were identified in the CSF of 1 of 8 patients. Electro- encephalograms were performed in 7 patients; 4 showed generalized slowing, and 1 showed focal discharges. None of the bacterial or fungal cultures was posi- tive. Table 2 lists the other microbiologic studies obtained. Viruses were not identified in any of the 34 cultures and in only 1 of the 38 PCR studies. Three Fig 1. Seasonal distribution of 18 cases of ADEM. respiratory secretions were obtained for fluorescent

e2 ACUTE DISSEMINATEDDownloaded ENCEPHALOMYELITIS from www.aappublications.org/news by guest on September 24, 2021 TABLE 2. Results of Microbiologic Studies IgG Bartonella henselae antibodies. A possible diagno- Studies Specimens Number sis of M pneumoniae disease was made in 1 patient Tested Positive with a history of a cough, wheezing, and pharyngitis Virus culture with IgG-specific mycoplasmal antibody. A second Throat/nasopharynx 11 0 possible diagnosis of rotavirus disease was estab- Stool 9 0 lished in 1 patient with vomiting and diarrhea. Four- CSF 14 0 teen patients did not have microbiologic diagnoses. PCR Throat/nasopharynx Enterovirus 6 0 Neuroimaging Mycoplasma 2 0 Epstein-Barr virus 1 1 All patients had head CT scans, which revealed Stool lesions in only 2 patients. One of these patients had Enterovirus 5 0 multiple supratentorial lesions with mild hypoden- CSF sity in the subcortical white matter and no associated Enterovirus 9 0 mass effect. These lesions were bilateral and asym- Herpes simplex virus 15 0 Ͻ Antibody metric, measuring 1 cm in diameter. Another pa- EBV VCA IgG 11 5 tient had mild unilateral brain swelling with mild EBV VCA IgM 10 1 associated mass effect and midline shift; no distinct M pneumoniae IgG 5 2 parenchymal foci of hypodensity were seen. This M pneumoniae IgM 1 0 Influenza 3 3 patient was treated initially as having herpes enceph- B henselae IgG 1 1 alitis. However, brain MRI subsequently showed B henselae IgM 1 1 multiple supratentorial lesions in the subcortical ELISA white matter of the left hemisphere with additional Rotavirus 2 2 lesions in the brainstem, suggesting multifocal in- VCA indicates viral capsid antigen; ELISA, enzyme-linked immu- volvement. MRI was performed in all but 1 patient, nosorbent assay. for whom the study was contraindicated because of the presence of a cardiac pacemaker. This patient antibody testing, and none was positive. Virus-spe- was identified above with multiple bilateral subcor- cific antibody was detected in 16 of 38 tests. A defi- tical lesions on the CT scan. nite microbiologic diagnosis of EBV was established Seventeen patients had T1, T2, FLAIR, and gado- in 1 patient. This patient presented with 5 days of linium-enhanced T1 images. MRI findings are sum- severe pharyngitis. Serologic studies demonstrated marized in Table 3. Information on the localization of IgG-specific seroconversion and the presence of IgM- lesions shown in detail in Table 4 and summarized specific EBV antibody. In addition, EBV DNA was below is from the 15 patients for whom MRI films detected in pharyngeal secretions by PCR. A proba- were available for direct rereview. A representative ble diagnosis of cat scratch disease was established in patient MRI scan is shown in Fig 2. All patients had a patient with a history of cat contact and IgM and multiple hyperintense brain lesions on T2/FLAIR

TABLE 3. Comparison of 3 Pediatric ADEM Studies Parameters Present Dale7 Hynson8 Demographics Study type Retrospective Retrospective Retrospective Geographical area USA UK Australia Number of patients 18 28 31 Age (y; range, mean) 2–22, 8 3–15, 7 2–16, 6 Seasonal clustering Yes Yes Not known Preceding infection (%) 72 74 77 Clinical findings (%) Motor signs 77 71 23 Altered consciousness 45 69 68 Fever 39 43 52 Cranial neuropathy 23 51 45 Seizures 17 17 13 Laboratory findings (%) Leucocytosis 39 64 62 CSF pleocytosis 69 64 62 Elevated CSF protein 55 60 45 MRI findings (%) White matter lesions 93 91 90 Thalamic lesions 27 41 32 Periventricuar lesions 60 44 29 Patients with follow-up MRI 81 30 25 Normal follow-up MRI 7 37 25 Treatment and outcome (%) High-dose steroids 21 87 74 Survival 100 100 100 Residual deficits 17 43 19 Relapses 0 25 12

Downloaded from www.aappublications.org/newshttp://www.pediatrics.org/cgi/content/full/110/2/ by guest on September 24, 2021 e1 e3 TABLE 4. Initial T2/FLAIR MRI Findings in 15 Patients With ADEM* Location of Hyperintense No. of Patients No. of Lesions Per Total No. of Lesions on T2/FLAIR (%) Patient (Mean Lesions in All [Range]) Patients (%) Frontal lobe 15 (100%) 8.0 (1–30) 120 (48%) Parietal lobe 14 (93%) 3.7 (0–18) 55 (22%) Temporal lobe 8 (53%) 1.2 (0–5) 18 (7%) Occipital lobe 6 (40%) 1.0 (0–6) 15 (6%) Cortical gray matter 12 (80%) 4.9 (0–28) 73 (29%) Subcortical white matter 14 (93%) 6.0 (0–44) 90 (36%) Periventricular white matter 9 (60%) 2.5 (0–16) 37 (15%) Internal capsule 1 (7%) 0.1 (0–2) 2 (0.8%) Thalamus 4 (27%) 0.3 (0–2) 5 (2%) Basal ganglia 3 (20%) 0.3 (02) 4 (1.6%) Brainstem 7 (47%) 1.1 (0–6) 16 (6%) Cerebellum 2 (13%) 0.1 (0–1) 2 (0.8%) Corpus callosum (Splenium) 1 (7%) 0.1 (0–2) 1 (0.4%) Total brain lesions 15 (100%) 16.8 (4–56) 252 (100%) * Data are from 15 patients for whom MRI films were available for detailed rereading.

Fig 2. MRI findings in 1 case demonstrating typical asymmetric supratentorial lesions (top row, initial study; bottom row, 8 weeks later). Lesions are bilateral cortical and subcortical, hyperintense on FLAIR (left) and mildly hypointense on noncontrast T1 (middle, arrow) with no mass effect. Postcontrast imaging (right) shows a variable enhancement pattern including homogeneous enhancement of 1 lesion and ring enhancement of another. Eight weeks later, the lesions are nearly resolved on noncontrast studies (bottom row); enhancement was no longer seen (not shown). images, with a mean of 16.8 lesions per patient parietal (22%), temporal (7%), and occipital (6%; Ta- (range: 4–56). Sixteen (94%) of 17 patients had corti- ble 4). Lesions were detected in the cerebral cortex in cal and/or subcortical white matter lesions. The le- 80%, in subcortical white matter in 93%, in periven- sions were asymmetric in location and size. In 2 tricular white matter in 60%, in deep gray matter patients, predominantly unilateral involvement of (basal ganglia or thalamus) in 47%, and in brainstem the cortical gray and subcortical white matter was in 47% of patients. The internal capsule, cerebellum, noted. A total of 252 lesions were seen in the brain and corpus callosum were only rarely involved (Ta- (mean: 16.8 per patient; range: 4–56; Table 4). Most ble 4). On noncontrast T1-weighted images, only 2 lesions were 1 ϫ 1 cm in diameter or slightly less but lesions were hypointense; all others were isointense. in some cases were up to 5 cm in diameter. All There was no heterogeneous signal, T1 shortening, patients had supratentorial involvement. Regarding or T2 shortening in the lesions to suggest acute or lobar location, 48% of these were frontal, followed by subacute hemorrhage. Mild mass effect was present

e4 ACUTE DISSEMINATEDDownloaded ENCEPHALOMYELITIS from www.aappublications.org/news by guest on September 24, 2021 in only 2 cases but absent in all other cases. Gado- and none beyond 1 week. Five patients were venti- linium-enhanced studies were performed in 15 of 17 lated because of respiratory failure. Duration of ven- patients and enhancement was present in brain tilation ranged from 1 to 20 days. One patient pro- lesions of 4 patients. The enhancement patterns in gressed to a “locked-in syndrome” and remained in the brain ranged from homogeneous to heteroge- that state for nearly 2 weeks. He subsequently made neous or ring-like patterns (Fig 2). T1 enhancement a near total recovery except for minor gait difficulties was present in 7 patients, 5 of which occurred in and urinary incontinence. the spinal cord. Spinal cord involvement was typi- cally multisegmental with patchy enhancement. Fol- Treatment low-up MRI was performed in 14 patients from 2 Eleven patients (61%) were treated with steroids. weeks to 1.5 years after discharge from the hospital. Eight patients received prednisone at 2 mg/kg/d or Ten of the 14 follow-up MRI scans were done at 3 dexamethasone at 0.5 mg/kg/d for 5 to 7 days and months or less from the initial MRI. In only 1 of 14 tapered over 1 to 2 weeks. Three patients received patients did the MRI return to normal. In 8 patients, high-dose intravenous methylprednisolone of 20 the findings were improved both in number and in mg/kg/d within the first week of hospitalization for size of lesions. In 3 patients, the lesions were un- 5 days and tapered over 4 to 6 weeks. None of the changed. In 2 patients, new lesions were identified in patients on either steroid regimen experienced any follow-up scans before 8 weeks despite clinical re- adverse effects from steroids. Two patients also re- covery from the illness. These lesions were consid- ceived intravenous immunoglobulin (IVIG) at 400 ered part of the initial illness. mg/kg/d for 5 days. One of these patients received Spinal cord MRI generally revealed large confluent a second course of IVIG because he remained coma- intramedullary lesions extending over multiple seg- tose and quadriplegic 3 weeks into the illness. Seven ments of the spinal cord with variable enhancement. patients did not receive steroids or IVIG. Antibiotics Cervical and thoracic spinal cord MRI was per- were given to 15 patients, and acyclovir was given to formed in 8 patients, and 7 studies were available for 13 patients. One patient received ganciclovir for EBV rereview. Two patients had normal spinal MRI. Five infection. Treatment was continued until the throat patients had intramedullary lesions that were hyper- secretions were negative for EBV by PCR. Anticon- intense on T2-weighted images and isointense on vulsants were administered to 3 patients who had noncontrast T1-weighted images. One patient had 5 seizures during the course of their illnesses; 1 of lesions distributed throughout the cervical and tho- them required long-term anticonvulsant medication. racic cord and conus medullaris, with faint linear and patchy enhancement. Another patient had large Outcome confluent lesions with cord swelling at C2 to C7 with no enhancement; 1 week later, the lesions and swell- Deficits at Discharge ing were nearly resolved. A third patient had contig- All of the patients had clear sensorium at dis- uous cord lesions extending from C4 to the conus charge. Fifteen patients had neurologic deficits at medullaris with patchy enhancement but no cord discharge. Eight patients had gait disturbances. Four swelling. A fourth patient had a large confluent le- patients had paraparesis and/or urinary problems, sion from T2 to the conus with cord swelling but no and 1 patient had quadriparesis with urinary prob- enhancement; 3 months later, only a residual conus lems. One patient had resolving hemiparesis. One lesion remained. The fifth patient had contiguous patient had fatigue and headache. Three patients did lesions in the cord from C6 to the conus with heter- not have any deficits at the time of discharge from ogeneous and ring enhancement and swelling of the the hospital. conus. One patient had recurrence of gait symptoms and Deficits at Follow-up urinary retention at 9 months from the initial presen- All 18 patients had been seen at follow-up. The tation. A repeat MRI showed complete disappear- duration of follow-up ranged between 2 months and ance of previous lesions, but new lesions appeared in 60 months with a mean of 22 months. Thirteen pa- different locations. This patient had no evidence of tients who had deficits at discharge were functioning further recurrence in the past 4 years. Another pa- normally without any deficits at the 3-month follow- tient had a repeat MRI at 18 months because of up. Of the remaining 5 patients who had deficits at continuing seizures. This patient had new lesions in the 3-month follow-up, 2 improved and only 3 pa- the subcortical white matter of the contralateral side tients had continuing deficits. Two of these patients with atrophy of the previously involved hemisphere. had residual urinary symptoms and gait problems. The new lesions were asymptomatic. However, a Both of these patients had severe spinal cord disease putative diagnosis of multiple sclerosis (MS) remains at presentation. Another patient had recurrence of a consideration in both of the patients. symptoms 9 months after initial hospitalization. He had new hyperintense lesions on T2/FLAIR at recur- Hospital Course rence. The initial lesions had completely resolved. He Duration of hospitalization ranged from 2 days to had returned to his baseline function before this 94 days with a mean of 14.5 days and a median of 6 recurrence. Although he improved with repeat high- days. Twelve patients had maximum deficits at ad- dose methylprednisolone treatment, he continued to mission. Six patients had deterioration in their neu- have mild gait difficulties and urinary symptoms. rologic status during the first week of hospitalization No further recurrences occurred for 4 years. The

Downloaded from www.aappublications.org/newshttp://www.pediatrics.org/cgi/content/full/110/2/ by guest on September 24, 2021 e1 e5 third patient had continuing seizures and needed diagnosis.7,22 A second attack of MS occurs over a anticonvulsant medication. This patient had pre- period of months to several years in children; there- dominantly unilateral lesions on the initial MRI. Re- fore, establishing a diagnosis of MS may require peat MRI 18 months after the initial diagnosis prolonged follow-up.23 In the absence of clinical re- showed atrophy and encephalomalacia in the left currence, new MRI lesions that appear beyond the temporal lobe and new hyperintense lesions on T2 first few months after ADEM may help in the early FLAIR in the cortical gray and subcortical white diagnosis of MS.23 This is important, as the early matter on the contralateral side. However, she did treatment of MS has been shown to prevent the not have any new neurologic symptoms, and the progression of the disease.24 new lesions were asymptomatic. The present study also confirmed the overall good outcome observed in the British and Australian re- DISCUSSION ports. One hundred percent of children survived Eighteen cases of ADEM were identified during a ADEM in the 3 studies, and Ͼ80% of children were 6-year period in a single children’s hospital. The neurologically normal at the conclusion of follow-up results are consistent with findings in 2 other, similar in 2 studies (Table 3). In addition, relapses occurred reviews from the United Kingdom and Australia.7,8 in only 0% to 25% of patients. Most of the reported In all 3 studies, a nonspecific infectious disease pre- relapses occurred after the rapid weaning of high- ceded the onset of ADEM in Ͼ70% of cases (Table dose steroids. Although high-dose steroid therapy 3).7,8 Two of the 3 studies documented a seasonal was used in only 21% of the children in the present distribution of cases, further suggesting an infectious report, 74% and 88% of children received high-dose cause. Although a number of infectious agents, such steroids in the British and Australian studies, respec- as influenza, measles, mumps, rubella, varicella, her- tively. Despite these differences in treatment, neuro- pes simplex virus, hepatitis viruses, EBV, coxsack- logic outcome, relapse rates, and MRI findings at ieviruses, mycoplasma, Campylobacter, streptococ- follow-up were similar. It is difficult to assess the cus, legionella, and rickettsia, have been implicated actual benefits of steroid therapy in ADEM because in ADEM, only influenza is associated with the win- none of the 3 studies was prospective or designed to ter/spring respiratory illness pattern observed in the evaluate therapy. present report.9–19 Despite vigorous attempts to identify microbial pathogens in the present study, CONCLUSION only 1 patient with EBV disease was classified with a The present study demonstrated that ADEM in definite microbiologic ADEM cause. Of the 2 patients children occurs in winter/spring and closely follows with rotavirus disease, 1 was classified as possibly an upper respiratory tract illness. MRI studies dem- associated with ADEM. Rotavirus typically occurs onstrate asymmetric lesions in the cortical and sub- during winter/spring but produces gastrointestinal cortical white matter of the brain. Initial lesions may rather than respiratory illness. A recent report, how- persist and new lesions may appear during the im- ever, described encephalopathy in 2 children with mediate recovery period. Clinical outcome, in gen- rotavirus diarrhea, and MRI findings in 1 of the 20 eral, is favorable regardless of therapy. A minority of children was consistent with ADEM. patients may subsequently be shown to have MS The vast majority of patients in the present study because of clinical and/or radiologic recurrence. had no microbiologic diagnosis despite numerous laboratory investigations. The failure to identify a viral agent suggests that the inciting agent or agents REFERENCES are unusual or cannot be recovered by standard lab- 1. Lucas J. An account of uncommon symptoms succeeding the measles with additional remarks on the infection of measles and smallpox. oratory procedures. The list of potential winter/ London Med J. 1790;11:325–331 spring respiratory pathogens includes influenza, re- 2. McAlpine D. 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Downloaded from www.aappublications.org/news by guest on September 24, 2021 Acute Disseminated Encephalomyelitis in Children S. N. Krishna Murthy, Howard S. Faden, Michael E. Cohen and Rohit Bakshi Pediatrics 2002;110;e21 DOI: 10.1542/peds.110.2.e21

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